The designation "lectin" is derived from the property of certain proteins to "select" (i.e. recognize) specific carbohydrate structures and to form a lectin-carbohydrate complex.
Lectins can be defined as follows:
the recognition of carbohydrates is highly specific and thus comparable to the antigen-specificity of antibodies or the substrate-specificity of enzymes; PA0 in contrast to antibodies which can also specifically recognize carbohydrate-residues of glycoconjugates, lectins are of non-immune origin; PA0 in contrast to enzymes which can also specifically recognize carbohydrates or glycoconjugates, lectins do not display any detectable enzymatic activity; PA0 they display carbohydrate-inhibitable homotypic and heterotypic agglutinating activity (see FIG. 1), e.g. of bacteria or blood cells as trypsinized and glutaraldehyde treated rabbit erythrocytes. PA0 the type of tumor as compared with the nontransformed cell type, PA0 the developmental stage or degree of differentiation of the particular tumor, PA0 the tissue environment of the particular tumor.
From this definition of lectins it can be taken that for the clear identification of a protein as a lectin, the properties of the protein have to fulfil all the above-mentioned prerequisites. Otherwise the protein in question could, for instance, also be an antibody or an enzyme.
The binding of lectins to their corresponding carbohydrates can be either Ca.sup.2+ -dependent or Ca.sup.2+ -independent, i.e. some of the lectins form a complex with the respective carbohydrate only in the presence of Ca.sup.2+ -ions.
Until very recently lectins were thought to be peculiarities of the plant kingdom. The physiological role of these proteins is still not known. During the last few years it has become apparent that lectins are regular components of almost every cell membrane or cell surface. Although not much is known yet in this field of research, it is suggested that lectins play a key role in many intercellular processes together with the corresponding carbohydrates on other cells. They form what is probably the most important cellular recognition and communication system and might be important in the development of organs, especially in the development of the central nervous system. Furthermore, they are believed to play a role in fertilization (when sperm and egg recognize each other) and are important in endocytosis; see Barondes, Ann. Rev. Biochem. 50 (1981), p. 207.
Gabius et al. (Hoppe-Seyler's Z. Physiol. Chem. 355 (1984), p. 633), describe Ca.sup.2+ -independent lectins which were isolated from bovine pancreas and have a molecular weight of 16,000, 35,000 and 64,000, respectively. They bind specifically the .beta.-galactosides lactose and asialofetuin and the .alpha.-galactoside melibiose. Furthermore, fucose-binding lectins which are Ca.sup.2+ -dependent and have a molecular weight of 34,000; 62,000; and 70,000; respectively, are described.
Ashwell et al. (Ann. Rev. Biochem. 51 (1982), p. 531) describe .beta.-galactoside-specific receptors of the liver which specifically recognize asialo-glycoside residues of proteins and are responsible for the uptake of these glycoproteins into hepatocytes. Furthermore, a hepatic mannan-specific receptor is described. J. Biochem. 94 (1983), p. 937 data of a protein with Ca.sup.2+ -dependent mannan-binding specificty. The protein was isolated from the mesenteric lymph nodes of rats and from human serum. It was, however, not analyzed according to the parameters given above, whether this protein actually is a lectin.
Rutherford et al. (FEBS Lett. 136 (1981), p. 105) describe the isolation and characterization of a mannan-binding lectin of the vitelline membrane of the early chick embryo. The physiological role of this protein, however, is not disclosed.
From a publication of Roberson and Barondes (J. Biol. Chem. 257 (1982), p. 7520) a lectin of Xenopus laevis oocytes, X. laevis embryos and the liver of the adult X. laevis is known. The lectin under investigation displays different specific activities in the three different differentiation stages.
Grabel et al. (Cell 17 (1979), p. 477) published the occurrence of a carbohydrate-binding component on the surface of teratocarcinoma stem cells. This component is designated by the authors as a lectin-like component and not as a lectin. Thus, this reference does not disclose whether or not the carbohydrate-binding component found is a lectin.
Moreover, this publication does not contain any characterizing data concerning the carbohydrate-binding component. What is disclosed there is just an observation on the association of cells, which can be inhibited by the addition of mannose-rich glycoproteins as yeast invertase, yeast, mannans and horse radish peroxidase. A further publication of Grabel et al. (Biophys., Biochem. Res. Comm. 102 (1981), p. 1165) refers to the extraction of mouse teratocarcinoma cells. According to the authors, this extract contains a fucoidan-inhibitable hemagglutination activity.
In the papers of Raz et al. (Cancer Res. 41 (1981), p. 3642), Roche et al. (J. Cell. Biochem. 22 (1983), p. 131) and Teichberg et al. (Proc. Natl. Acad. Sci. U.S.A. 72 (1975), p. 1383) a .beta.-galactoside specific hemagglutination activity, a glucose-specific endocytosis activity, and a .beta.-galactoside-specific hemagglutination activity, respectively, are described which were detected on the surface of tumor cells or in the extracts of tumor cells. It has to be understood, however, that the papers of Grabel et al. (supra), Raz et al. (supra), Roche et al. (supra), and Teichberg et al. (supra) do not show the presence of lectins on the surface or in the cytoplasm of tumor cells. The presence of lectins is only proved if all of the above-mentioned parameters characterizing a protein as a lectin are investigated. If such a complete characterization is not carried out, the carbohydrate-specific protein may also be an enzyme of the cellular carbohydrate and glycoconjugate metabolism, see e.g. Roseman (Chem. Phys. Lipids 5 (1970), p. 270). In this publication of Roseman, the occurrence of glycosyl-transferases as cell surface-exposed carbohydrate-specific proteins has been suggested. This hypothesis was confirmed by e.g. Rauvala et al. (Proc. Natl. Acad. Sci. U.S.A. 80 (1983), p. 3991).
Finally, lectins were identified in chicken liver and embryonic chicken muscle (Ceri et al., J. Biol. Chem. 256 (1981), p. 390; de Waard et al., J. Biol. Chem. 252 (1976), p. 5781), human lung (J. T. Powell, Biochem. J. 187 (1980), p. 123) and human liver (Wild et al., Biochem. J. 210 (1983), p. 167).
Thus, lectins of mammalian tumor cells have not been characterized.